This project will investigate the mechanisms of initiation, promotion and suppression of mammary tumors in the rat and will extend our analysis of the effects of prenatal exposure to diethylstilbestrol (DES) on mammary carcinogenesis. Some of the DES-exposed female rats will be treated postnatally with a carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA). Conditions and drugs which modify the endocrine status of the DES-exposed animals before DMBA treatment will be employed to determine the effects of reproductive history or altered hormone levels on mammary tumor incidence. The influence of prenatal exposure and postnatal treatment with estrogens on mammary tumor incidence will be compared in two different strains of rat. Data from these experiments will bear on the genetic aspects of susceptibility to tumor initiation. Transplacental exposure to DES in humans is associated with teratogenic and carcinogenic changes in the vagina and cervix. Whether breast tissue was also affected is not yet known. Therefore, experiments in this proposal provide a model system where the potential risk for breast cancer among DES-exposed women can be studied.